Stelzer Ina Annelies, Urbschat Christopher, Schepanski Steven, Thiele Kristin, Triviai Ioanna, Wieczorek Agnes, Alawi Malik, Ohnezeit Denise, Kottlau Julian, Huang Jiabin, Fischer Nicole, Mittrücker Hans-Willi, Solano Maria Emilia, Fehse Boris, Diemert Anke, Stahl Felix R, Arck Petra Clara
Division of Experimental Feto-Maternal Medicine, Department of Obstetrics and Fetal Medicine, University Medical Center Hamburg, Hamburg, Germany.
Department of Anesthesiology, Perioperative and Pain Medicine, Stanford University, Palo Alto, California, CA, USA.
Nat Commun. 2021 Aug 4;12(1):4706. doi: 10.1038/s41467-021-24719-z.
During mammalian pregnancy, immune cells are vertically transferred from mother to fetus. The functional role of these maternal microchimeric cells (MMc) in the offspring is mostly unknown. Here we show a mouse model in which MMc numbers are either normal or low, which enables functional assessment of MMc. We report a functional role of MMc in promoting fetal immune development. MMc induces preferential differentiation of hematopoietic stem cells in fetal bone marrow towards monocytes within the myeloid compartment. Neonatal mice with higher numbers of MMc and monocytes show enhanced resilience against cytomegalovirus infection. Similarly, higher numbers of MMc in human cord blood are linked to a lower number of respiratory infections during the first year of life. Our data highlight the importance of MMc in promoting fetal immune development, potentially averting the threats caused by early life exposure to pathogens.
在哺乳动物怀孕过程中,免疫细胞会从母体垂直转移至胎儿体内。这些母体微嵌合细胞(MMc)在后代中的功能作用大多尚不明确。在此,我们展示了一种小鼠模型,其中MMc数量正常或较低,这使得对MMc进行功能评估成为可能。我们报告了MMc在促进胎儿免疫发育方面的功能作用。MMc诱导胎儿骨髓中的造血干细胞在髓系区内优先分化为单核细胞。MMc和单核细胞数量较多的新生小鼠对巨细胞病毒感染表现出更强的抵抗力。同样,人类脐带血中较高数量的MMc与出生后第一年较低的呼吸道感染发生率相关。我们的数据突出了MMc在促进胎儿免疫发育方面的重要性,可能避免早期接触病原体所带来的威胁。